Sterilized chlorhexidine article and method of sterilizing a chlorhexidine article

ABSTRACT

A sterilized chlorhexidine product for topical disinfection includes a package and at least one sterilized chlorhexidine article comprising a cloth. The package includes a film defining an interior volume and the sterilized chlorhexidine article disposed within the interior volume. The package further includes a first sealed end portion positioned at a first end of the film and a second sealed end portion positioned at a second end of the film, wherein the first sealed end portion and the second sealed end portion define a hermetically sealed portion about the interior volume.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/557,160, filed on Aug. 30, 2019, which is a continuation of U.S.patent application Ser. No. 16/231,034, filed on Dec. 21, 2018, which isa continuation of U.S. patent application Ser. No. 15/360,037, filed onNov. 23, 2016, which claims priority to and the benefit of U.S. patentapplication Ser. No. 62/259,727, filed on Nov. 25, 2015. The entirecontents of each are hereby incorporated by reference.

BACKGROUND

The embodiments described herein relate to a sterilized chlorhexidinearticle and a method of sterilizing a chlorhexidine article.

Healthcare-associated infections (HAI's), which are infectionscontracted during the course of treatment for a medical or surgicalcondition, are a significant problem worldwide. HAI's are often causedby pathogenic microorganisms colonizing the patient's skin, mucousmembranes, or hollow viscera. Surgery, trauma, and indwelling devicescause a breach in the body's natural barriers thereby providing apathway for such pathogens to colonize and infect normally sterile areasof the body.

Measures to reduce colonization with pathogens have proven effective inreducing HAI's. One measure to reduce pathogens on the skin and mucousmembranes is the topical application of antiseptics such aschlorhexidine. A convenient and effective means of applyingchlorhexidine to the skin or mucous membranes is with the use of anapplicator. For example, among their many uses, applicators may be usedto apply chlorhexidine to decolonize the skin or mucous membranes of apatient or a healthcare worker prior to a surgical procedure to helpprevent a surgical site infection, or they may be used ion hospitalizedpatients with indwelling devises such as central venous catheters,urinary catheters, or endotracheal tubes to routinely decolonize thepatient's skin or mucous membranes to help prevent self-infection.

It has been a challenge to develop a chlorhexidine article, and a methodof sterilizing a chlorhexidine article.

SUMMARY

In one embodiment, a sterilized chlorhexidine product is provided. Thesterilized chlorhexidine product comprises a package defining aninterior volume. The sterilized chlorhexidine product further comprisesa sterilized chlorhexidine article. The sterilized chlorhexidine articlecomprises a sterilized applicator and a sterilized antisepticcomposition impregnated in the sterilized applicator. The sterilizedantiseptic composition comprises a sterilized solvent. The sterilizedantiseptic composition further comprises a sterilized antibacterialagent dissolved in the sterilized solvent. The sterilized applicator andthe sterilized antiseptic composition are disposed in the interiorvolume of the package. The sterilized chlorhexidine article has aSterility Assurance Level of from 10⁻³ to 10⁻⁹.

The present disclosure also provides a method of sterilizing achlorhexidine article. The method comprises providing an applicator. Themethod further comprises providing an antiseptic composition comprisinga solvent and an antibacterial agent dissolved in the solvent. Themethod further comprises sealing the chlorhexidine article inside thepackage to form a chlorhexidine product. The method further comprisescooling the chlorhexidine product. The method further comprisessterilizing the chlorhexidine product to form a sterilized chlorhexidinearticle.

BRIEF DESCRIPTION OF THE FIGURES

Advantages of the present invention will be readily appreciated as thesame becomes better understood by reference to the following detaileddescription when considered in connection with the accompanying drawingswherein:

FIG. 1 is a top view of a sterilized chlorhexidine product in accordancewith one embodiment.

FIG. 2 is a side view of the sterilized chlorhexidine product of FIG. 1.

FIG. 3 is a cross-sectional view of the sterilized chlorhexidine productof FIG. 1 including a plurality of sterilized chlorhexidine articles.

FIG. 4 is an expanded view of one of the plurality of sterilizedchlorhexidine articles of FIG. 3.

FIG. 5 is a top view of a shipping container containing a plurality ofthe sterilized chlorhexidine products of FIG. 1.

FIG. 6 is a cross-sectional view of the shipping container of FIG. 6.

FIG. 7A is a perspective view of a conveyor mechanism including ashipping container, a cooling unit, and a radiation unit.

FIG. 7B is a perspective view of the conveyor mechanism of FIG. 7A witha chlorhexidine product in place of the shipping container.

DETAILED DESCRIPTION

In one embodiment, as shown in FIGS. 1, 2, 3, and 4, a sterilizedchlorhexidine product 10 comprises a package 12 and a chlorhexidinearticle 14. The package 12 defines an interior volume 16. Thechlorhexidine article 14 is removably disposed in the interior volume 16of the package 12.

In some embodiments, the package 12 comprises a film 18 having sealedend portions 20 as shown in FIG. 1. The package 12 may have arectangular geometry. Of course, it is contemplated the package 12 mayhave any geometrical configuration suitable for receiving thechlorhexidine article 14 such as, by way of non-limiting example, arectangular geometry.

Referring to FIGS. 1 and 3, in the illustrated embodiment, the film 18and the sealed end portions 20 form a hermetic seal about the interiorvolume 16 and the chlorhexidine articles 14 disposed therein. In thismanner, the package 12 protects the chlorhexidine articles 14 fromcontamination because the chlorhexidine articles 14 are not exposed tothe environment outside the package 12. Thus, the package 12 isparticularly suitable for terminal sterilization processes such as thosedescribed in detail below. While a specific configuration of the packageis described, it is contemplated that the package may be adapted basedon the configuration of the chlorhexidine articles 14 disposed therein.

In some embodiments, the package may further comprise a tear seal thatfacilitates access to the chlorhexidine articles disposed in thepackage. The tear seal may be arranged on the package such that the tearseal does not compromise the hermetic seal formed by the film and thesealed end portions. In this manner, the package may hermetically sealthe chlorhexidine articles disposed therein and also allow a patientcare provider to easily access the chlorhexidine articles.

In other embodiments, the film may define an outlet for dispensing thechlorhexidine articles disposed within the package. The package mayfurther comprise a label for the outlet. The label may be applied to anexternal surface of the package over the outlet. The label may have afree or non-adhered end for peeling the label to expose the outlet. Ofcourse, it will be appreciated that when the package comprises an outletand a label, the package may not hermetically seal the chlorhexidinearticles and thus may not be suitable for terminal sterilizationprocesses.

In certain embodiments, one or more chlorhexidine articles 14 may bedisposed in the interior volume 16 of the package 12. The number ofchlorhexidine articles 14 disposed into each package 12 is notparticularly limited, and may correspond to the desired dosage ofantiseptic intended to be delivered to the patient. In otherembodiments, a single chlorhexidine article 14 is disposed in theinterior volume 16 of the package 12. More particularly, in someembodiments, the number of chlorhexidine articles 14 disposed in thepackage 12 may be the same as the number of chlorhexidine articles 14that are used for a particular task. As an example, when the particulartask requires six chlorhexidine articles 14, six chlorhexidine articles14 may be disposed in each package. In this manner, a patient careprovider will be discouraged from using either too many, or too few,chlorhexidine articles 14 for the particular task. In other embodiments,the one or more of chlorhexidine articles 14 disposed in the package maybe of from 2 to 10, of from 2 to 8, of from 2 to 6, or of from 2 to 4.In one embodiment, two chlorhexidine articles 14 are disposed in eachpackage 12. With reference to FIG. 2, in the illustrated embodiment, tenchlorhexidine articles 14 are disposed in the package 12. Of course,still other quantities of chlorhexidine articles 14 may be disposed ineach package 12. It should be appreciated that in other instances, thechlorhexidine articles 14 are not disposed within the interior volume 16of the package 12, but may be prevented from exposure to the externalenvironment through other means.

With reference to FIGS. 5 and 6, in some embodiments, a one or more ofchlorhexidine products 10 may be disposed in a shipping container 22,such as a cardboard box 22. The number of chlorhexidine products 10disposed in the shipping container 22 is advantageously selected basedon the type of sterilizing process to be applied. For example, theshipping container may comprise of from 5 to 50 chlorhexidine products10. In other embodiments, the shipping container 22 may comprise fewerthan twenty sterilized chlorhexidine products 10 to permit sterilizationof all chlorhexidine articles 14 disposed therein. In still otherembodiments, the shipping container may comprise of from 40 to 150sterilized chlorhexidine products 10. Of course, still other quantitiesof sterilized chlorhexidine products 10 may be disposed in the shippingcontainer 22.

It should be appreciated that the present disclosure describes a methodof sterilizing a chlorhexidine product to form a sterilizedchlorhexidine article. As such, throughout this disclosure, descriptionthat accompanies the terms the chlorhexidine article, or components andcompositions thereof, may be referred to as the ‘sterilized’ componentor composition upon being exposed to suitable processing where suchsterility can be validated. By way of non-limiting example, thesterility of the chlorhexidine article may be validated in accordancewith ISO 11137.

In certain embodiments, the sterilized chlorhexidine article is intendedto be used by a patient care provider for disinfecting skin or mucousmembranes of a patient, such as disinfecting skin or mucous membranes ofthe patient prior to surgery or to routinely disinfect the skin duringhospitalization. Alternatively, the sterilized chlorhexidine article maybe used to maintain hygiene of a patient, particularly a patient unableto shower or bathe.

With reference to FIG. 4, the chlorhexidine article 14 comprises anapplicator 24 and an antiseptic composition. The applicator 24facilitates topical application of the antiseptic composition to theskin or mucous membranes of a patient. As such, the applicator 24 maytake any form suitable for topically applying the antiseptic compositionto the skin or mucous membranes of a patient. Characteristics that maybe considered when determining whether an applicator 24 is suitableinclude, by way of non-limiting example, porosity, absorbency, skin ormucous membrane contactable surface area, biocompatibility, ability ofthe applicator to retain the antiseptic composition, cost of production,etc. By way of non-limiting example, suitable examples of the applicator24 include a cloth, a foam, a brush, a squirt bottle, a roller, etc.

In certain embodiments, the applicator 24 may be suitable forimpregnation with the antiseptic composition such that the antisepticcomposition remains dispersed in the applicator until the chlorhexidinearticle 14 is applied to the skin or mucous membranes of a patient. Inthis manner, the antiseptic composition of the chlorhexidine article 14remains impregnated in and retained by the applicator 24 when thechlorhexidine article 14 is disposed within the package 12. When theapplicator 24 is applied to the skin or mucous membranes of the patient,the antiseptic composition is transferred from the applicator 24 to theskin or mucous membranes of the patient.

In some embodiments, the applicator may further comprise a receptaclefor receiving the antiseptic composition. When the applicator comprisesa receptacle, the antiseptic composition may be received in thereceptacle. The antiseptic composition received in the receptacle may besubsequently impregnated in the applicator by a patient care providerwhen the chlorhexidine article is being used to disinfect the skin ormucous membranes of a patient. In this manner, the antisepticcomposition does not need to be impregnated in and retained by theapplicator prior to disposing the chlorhexidine article in the package.In such embodiments, a barrier may be positioned between the applicatorand the receptacle that may be compromised upon activation by thepatient care provider.

With reference to FIG. 4, in one embodiment, the applicator 24 maycomprise a cloth 24. The cloth 24 may be woven, knitted, non-woven,velour, felt, flocked, needle-punched, tufted, stitch bonded,fusion-bonded, or combinations thereof. Of course, still other types ofcloth are contemplated. The cloth 24 may have any weight suitable forapplying the antiseptic composition to the skin or mucous membranes ofthe patient such as, by way of non-limiting example, of from 3.0 to 7.0,of from 4.0 to 6.0, or of from 4.5 to 5.5, ounce per square yard. Thecloth 24 may have a tensile strength suitable for applying theantiseptic composition such as, by way of non-limiting example, at least15, at least 20, or at least 25, pounds per inch in a given direction,with the given direction correlating to a machining direction of thecloth 24. The cloth 24 may have any thickness suitable for applying theantiseptic composition to the skin or mucous membranes of a patient suchas, by way of non-limiting example, of from 0.035 to 0.145, of from 0.45to 0.135, of from 0.055 to 0.125, of from 0.075 to 0.115, or of from0.085 to 0.105 inches.

In some embodiments, the cloth 24 is disposable. When the cloth 24 isdisposable, the cloth 24 may be disposed of after use so as to minimizethe chance of contaminating the skin or mucous membranes of a patientduring re-use. Of course, in other embodiments, the cloth 24 isre-usable.

The cloth 24 may comprise a first fiber. The first fiber may be asynthetic fiber or a natural fiber. When the first fiber is a syntheticfiber, the first fiber may be selected from the group comprisingpolyester fiber, polypropylene fiber, polyethylene fiber, rayon fiber,nylon fiber, acrylic fiber, acetate fiber, spandex fiber, latex fiber,Kevlar fiber, or combinations thereof. Of course still other types ofsynthetic fiber are contemplated such as, by way of non-limitingexample, polyamide fiber, azlon fiber, modacrylic fiber, novoloid fiber,nytril fiber, saran fiber, vinal fiber, vinyon fiber, regeneratedcellulose fiber, and cellulose acetate fiber. In instances where thefirst fiber comprises a natural fiber, the first fiber may be selectedfrom the group comprising cotton fiber, wool fiber, silk fiber, jutefiber, and linen fiber. Of course, still other types of natural fiberare contemplated.

In some embodiments, the cloth 24 may comprise a second fiber inaddition to the first fiber. The second fiber may comprise any of thematerials contemplated for the first fiber. When present, the secondfiber may be different from the first fiber or the same as the firstfiber. For example, the first fiber may be polyester fiber and thesecond fiber may be polyester fiber. Alternatively, the first fiber maybe polyester fiber and the second fiber may be polypropylene fiber. Ofcourse, still other combinations of the first fiber and second fiber arecontemplated. Moreover, it is contemplated that the cloth may comprisethree or more fibers comprising any of the materials contemplated forthe first fiber.

When present, the second fiber may be different from the first fiber orthe same as the first fiber. For example, the first fiber may bepolyester fiber and the second fiber may be polyester fiber.Alternatively, the first fiber may be polyester fiber and the secondfiber may be polypropylene fiber. Of course, still other combinations ofthe first fiber and second fiber are contemplated.

In one embodiment, the first fiber has a length of from 1.0 to 3.0inches. In another embodiment, the first fiber has a length of from 1.0to 2.0 inches. In other embodiments, the first fiber has a length offrom 0.5 to 6.0, of from 0.5 to 5.0, of from 0.5 to 4.0 or from 0.5 to3.0, inches. In still other embodiments, the first fiber has a length offrom 2.0 to 6.0, of from 3.0 to 6.0, of from 4.0 to 6.0, or of from 5.0to 6.0, inches. In still other embodiments, the first fiber has a lengthof from 0.5 to 2.5, of from 0.75 to 2.25, of from 1.0 to 2.0, or of from1.25 to 1.75, inches. Of course, still other lengths of the first fiberare contemplated.

In one embodiment, the second fiber has a length of from 2.0 to 4.0inches. In another embodiment, the second fiber has a length of from 2.5to 3.5 inches. In other embodiments, the second fiber has a length offrom 1.0 to 5.0, of from 2.0 to 5.0, of from 3.0 to 5.0, or of from 4.0to 5.0, inches. In still other embodiments, the second fiber has alength of from 1.0 to 4.0, 1.0 to 3.0, or of from 1.0 to 2.0 inches. Instill other embodiments, the second fiber has a length of from 2.25 to3.75, of from 2.5 to 3.5, or of from 2.75 to 3.25 inches. Of coursestill other lengths of the second fiber are contemplated. It will bereadily appreciated that the second fiber may have the same length asthe first fiber, or within any of the ranges described herein for thefirst fiber. Moreover, the first fiber may have a length within any ofthe ranges described herein for the second fiber.

In one embodiment, the first fiber may have a denier of from 0.5 to 2.5.In another embodiment, the first fiber may have a denier 1.0 to 2.0. Inother embodiments, the first fiber may have a denier of from 0.75 to2.5, of from 1 to 2.5, of from 1.25 to 2.5, of from 1.5 to 2.5, of from1.75 to 2.5, of from 2.0 to 2.5, or of from 2.25 to 2.5. In still otherembodiments, the first fiber may have a denier of from 0.5 to 2.25, offrom 0.5 to 2.0, of from 0.5 to 1.75, of from 0.5 to 1.5, of from 0.5 to1.25, of from 0.5 to 1.0, or of from 0.5 to 0.75. In still otherembodiments, the first fiber has a denier of from 0.8 to 1.5, or of from1.0 to 1.3. Of course, still other deniers of the first fiber arecontemplated.

In one embodiment, the second fiber may have a denier of from 4.5 to5.0. In another embodiment, the second fiber may have a denier of from4.0 to 6.0. In other embodiments, the second fiber may have a denier offrom 4.25 to 6.0, of from 4.5 to 6.0, of from 4.75 to 6.0, of from 5.0to 6.0, of from 5.25 to 6.0, of from 5.5 to 6.0, or of from 5.75 to 6.0.In still other embodiments, the second fiber may have a denier of from4.0 to 5.75, of from 4.0 to 5.5, of from 4.0 to 5.25, of from 4.0 to5.0, of from 4.0 to 4.75, of from 4.0 to 4.5, or of from 4.0 to 4.25. Instill other embodiments, the second fiber may be have a denier of from4.0 to 5.0, or of from 4.25 to 5.0. Of course, still other deniers ofthe second fiber are contemplated. It will be readily appreciated thatthe second fiber may have the same denier as the first fiber, or withinany of the ranges described herein for the first fiber. Moreover, thefirst fiber may have a denier within any of the ranges described hereinfor the second fiber.

In some embodiments, when the cloth comprises the first fiber and thesecond fiber, the first fiber may be included in an amount of from 40 to99, of from 50 to 90, of from 60 to 80, or of from 65 to 75, wt. % basedon the total weight of the cloth, and the second fiber may be includedin an amount of from 1 to 60, of from 10 to 50, of from 20 to 40, or offrom 25 to 35, wt. % based on the total weight of the cloth. In otherembodiments, the first fiber and the second fiber may be included in thesame amount. In still other embodiments, the first fiber and the secondfiber are not included in the same amount.

In one specific embodiment, the cloth 24 comprises the first fiber andthe second fiber, with the first fiber comprising polyester fiber andthe second fiber comprising polyester fiber. The first fiber has alength of from 1.0 to 3.0 inches and a denier of from 1.2 to 2.0. Thesecond fiber has a length of from 3.0 to 4.0 inches and a denier of from4.0 to 5.0. The first fiber is included in an amount of from 60 to 80wt. % based on the total weight of the cloth 24. The second fiber isincluded in an amount of from 20 to 40 wt. % based on the total weightof the cloth 24. The cloth 24 has a thickness of from 0.055 to 0.125.The cloth 24 has a weight of from 3.8 to 5.8 ounces per square yard. Thecloth 24 has a tensile strength of at least 27 pounds per square inch ina given direction, with the given direction correlating with a machiningdirection of the cloth 24.

When the applicator 24 comprises the non-woven cloth 24, the non-wovencloth 24 may be produced using any suitable method of producing anon-woven cloth as described herein. When the non-woven cloth 24comprises a first fiber and a second fiber, the method of making thenon-woven cloth may comprise blending the first and second fibertogether to form blended fibers. The method may further comprise cardingthe blended fibers to form carded fibers, followed by crosslapping andthen needle punching of the carded fibers to form a sheet of non-wovencloth. Thus, the first fiber and the second fiber are mechanicallyintertwined by needle punching. The sheet of non-woven cloth may then becut into individual non-woven cloths. The non-woven cloth may, by way ofnon-limiting example, have a length of from 5 to 15 inches and a widthof from 5 to 15 inches. In some embodiments, the length of the non-wovencloth may be equal to the width of the non-woven cloth. In otherembodiments, the length and the width may be different. Of course, stillother methods of producing the non-woven cloth 24 are contemplated.

In some embodiments, the method of producing a non-woven cloth mayfurther comprise folding the sheet of non-woven cloth. By way ofnon-limiting example, the non-woven cloth may be folded in a “z-fold”(also known as an “s-fold”), a “c-fold,” or any other fold stylesuitable for the non-woven cloth. With reference to FIGS. 3 and 4, inthe illustrated embodiment, the non-woven cloth 24 is folded in a“z-fold.” Of course, it is contemplated that in some embodiments thenon-woven cloth may not be folded.

As described above, the applicator may comprise foam. The foam maycomprise an open-celled foam or a closed-cell foam. The foam maycomprise synthetic polymers. In some embodiments, when the foamcomprises synthetic polymers, the synthetic polymers may be selectedfrom the group comprising polyurethanes, polyesters, polyalkylenes,polyols, or combinations thereof. Of course, still other syntheticpolymers are contemplated. Additionally, the foam may comprise naturalpolymers in other embodiments.

The antiseptic composition comprises one or more antibacterial agentsand one or more solvents. As such, when applied to the skin or mucousmembranes of a patient, the antiseptic composition is capable of killingor inhibiting the growth of bacteria on the skin or mucous membranes ofthe patient. In this manner, the antiseptic composition is suitable fordisinfecting the skin or mucous membranes of a patient, particularlyprior to a surgical operation.

The antibacterial agent may comprise chlorhexidine. The chlorhexidinemay be free base chlorhexidine or a pharmaceutically acceptable salt ofchlorhexidine. When the chlorhexidine is a pharmaceutically acceptablesalt of chlorhexidine, the chlorhexidine may be, chlorhexidinedihydrochloride, chlorhexidine diacetate, chlorhexidine digluconate(also known as chlorhexidine gluconate, or CHG), chlorhexidinedilactate, chlorhexidine digalactate, or combinations thereof. Incertain embodiments, the antibacterial agent is CHG. Thepharmaceutically acceptable salt of chlorhexidine may be selected basedon the solvent of the antiseptic composition due to the solubilityproperties of the pharmaceutically acceptable salt of chlorhexidine. Forinstance, CHG is soluble in water whereas chlorhexidine diacetate issubstantially insoluble in water and is therefore more suitable fornon-aqueous solvents.

It will be appreciated that the antibacterial agent may comprisecompounds other than chlorhexidine such as, by way of non-limitingexample, aminoglycoside compounds, polyhexanide, triclosan, quaternaryammonium compounds such as cetrimide, proflavine hemisulphate,chlorocresol, chlorophene, chloroxylenol, iodine, iodophors, etc., andcombinations thereof. Of course, still other antibacterial agents arecontemplated. Thus, while the term ‘chlorhexidine’ is used as anadjective throughout this disclosure to describe the product, articleand other components thereof, it should be appreciated thatproducts/articles may be free from chlorhexidine components if otherantibacterial agents are utilized.

The antibacterial agent may be included in the antiseptic composition inan amount of from 0.1 to 10 wt. % based on the total weight of theantiseptic composition. In another embodiment, the antibacterial agentmay be included in an amount of from 1.5 to 5.0 wt. % based on the totalweight of the antiseptic composition. In other embodiments, theantibacterial agent may be included in an amount from 0.5 to 10, of from1.0 to 10, of from 1.5 to 10, of from 2.0, to 10, of from 2.5 to 10, offrom 3.0 to 10, of from 3.5 to 10, of from 4.0 to 10, of from 4.5 to 10,of from 5.0 to 10, of from 5.5 to 10, of from 6.0 to 10, of from 6.5 to10, of from 7.0 to 10, of from 7.5 to 10, of from 8.0 to 10, of from 8.5to 10, of from 9.0 to 10, or of from 9.5 to 10 wt. % based on the totalweight of the antiseptic composition. In still other embodiments, theantibacterial agent may be included in the antiseptic composition in anamount of from 0.1 to 9.5, of from 0.1 to 9.0, of from 0.1 to 8.5, offrom 0.1 to 8.0, of from 0.1 to 7.5, of from 0.1 to 7.0, of from 0.1 to6.5, of from 0.1 to 6.0, of from 0.1 to 5.5, of from 0.1 to 5.0, of from0.1 to 4.5, of from 0.1 to 4.0, of from 0.1 to 3.5, of from 0.1 to 3.0,of from 0.1 to 2.5, of from 0.1 to 2.0, of from 0.1 to 1.5, of from 0.1to 1.0, or of from 0.1 to 0.5, wt. % based on the total weight of theantiseptic composition. In still other embodiments, the antibacterialagent may be included in the antiseptic composition in an amount of from0.5 to 8.0, of from 1.0 to 6.0, of from 1.5 to 5.0, of from 1.8 to 4.5,of from 1.8 to 3.5, or of from 1.8 to 2.5, wt. % based on the totalweight of the antiseptic composition. The amount of antibacterial agentmay vary outside of the ranges above, but is typically both whole andfractional values within these ranges. Further, it is to be appreciatedthat more than one antibacterial agent may be included in the antisepticcomposition, in which case the total amount of all the antibacterialagents included is within the above ranges.

The solvent may comprise an aqueous solvent, a non-aqueous solvent, orcombinations thereof. In certain embodiments, when the solvent comprisesan aqueous solvent, the solvent may be water. The water may be distilledwater, sterile water, purified water prepared in accordance with UnitedStates Pharmacopeia (USP) standards, or any other type of water that issuitable for use in antiseptic compositions.

In other embodiments, when the solvent is a non-aqueous solvent, thesolvent may be an alcohol. Examples of alcohols suitable for theantiseptic composition include, by way of non-limiting example, ethanolor isopropyl alcohol. Of course, still other solvents are contemplated.

The solvent may be included in the antiseptic composition in an amountof at least 1 wt. % based on the total weight of the antisepticcomposition. In another embodiment, the solvent may be included in theantiseptic composition an amount of at least 50 wt. % based on the totalweight of the antiseptic composition. In other embodiments, the solventmay be included in the antiseptic composition in amount of at least 5,at least 10, at least 20, at least 30, at least 40, at least 50, atleast 60, at least 70, at least 80, at least 90, at least 95, or atleast 99, wt. % based on the total weight of the antiseptic composition.In still other embodiments, the solvent may be included in theantiseptic composition in an amount less than 99, less than 95, lessthan 90, less than 80, less than 70, less than 60, less than 50, lessthan 40, less than 30, less than 20, less than 10, or less than 5, wt. %based on the total weight of the antiseptic composition. In still otherembodiments, the solvent is included in an amount of from 40 to 99, offrom 50 to 95, of from 60 to 90, of from 65 to 85, or of from 75 to 85wt. % based on the total weight of the antiseptic composition. Theamount of solvent may vary outside of the ranges above, but is typicallyboth whole and fractional values within these ranges. Further, it is tobe appreciated that more than one solvent may be included in theantiseptic composition, in which case the total amount of all thesolvents included is within the above ranges.

In certain embodiments, when the solvent is water, water may be includedin the antiseptic composition in an amount of at least 50 wt. % based onthe total weight of the antiseptic composition. In another embodiment,water may be included in the antiseptic composition in an amount of atleast 60 wt. % based on the total weight of the antiseptic composition.In other embodiments, water may be included in the antisepticcomposition in an amount of at least 65, at least 70, at least 75, or atleast 80, wt. % based on the total weight of the antiseptic composition.In still other embodiments, water may be included in the antisepticcomposition in an amount of from 50 to 99, of from 60 to 95, of from 70to 90, of from 75 to 90, or of from 80 to 90, wt. % based on the totalweight of the antiseptic composition. The amount of water may varyoutside of the ranges above, but is typically both whole and fractionalvalues within these ranges. Further, it is to be appreciated that morethan one type of water may be included in the antiseptic composition, inwhich case the total amount of all the types of water included is withinthe above ranges.

In some embodiments, at least 95% of the antibacterial agent isdissolved in the solvent of the antiseptic composition. In otherembodiments, at least 50, 60, 70, 80, 90, 99, wt. % of the antibacterialagent is dissolved in the solvent of the antiseptic composition. It isfurther contemplated that all of the antibacterial agent may bedissolved in the solvent of the antiseptic composition.

The antiseptic composition may further comprise a humectant. Thehumectant may be compatible for use in the antiseptic composition,particularly in view of the antibacterial agent included in theantiseptic composition. The humectant may be, by way of non-limitingexample, glycerol prepared according to USP standards (USP glycerol),propylene glycol, polyethylene glycol, N-methyl pyrrolidone, N-ethylpyrrolidone, diacetone alcohol, γ-butyryl lactone, ethyl lactate, lowmolecular weight polyethylene glycol, and combinations thereof. Incertain embodiments, the humectant comprises USP glycerol and propyleneglycol. Of course, other types of humectants are contemplated such as,by way of non-limiting example, monosaccharides, disaccharides, castoroil and derivatives and salts thereof, vegetable oil extracts such astriglycerides, and combinations thereof. Of course, still otherhumectants are contemplated.

When present, the humectant may be included in the antisepticcomposition in an amount less than 20 wt. % based on the total weight ofthe antiseptic composition. In another embodiment, the antisepticcomposition is included in an amount of from 3.0 to 10 wt. % based onthe total weight of the antiseptic composition. In other embodiments,the humectant is included in the antiseptic composition in an amountless than 17.5, less than 15, less than 12.5, less than 10, less than7.5, less than 5.0, or less than 2.5, wt. % based on the total weight ofthe antiseptic composition. In still other embodiments, the humectant isincluded in an amount of at least 2.5, at least 5.0, at least 7.5, atleast 10, at least 12.5, at least 15, at least 17.5, or at least 20, wt.% based on the total weight of the antiseptic composition. In stillother embodiments, the humectant is included in the antisepticcomposition in an amount of from 3.5 to 9.0, of from 4.0 to 8.0, of from4.5 to 7.0, or of from 5.0 to 6.0, wt. % based on the total weight ofthe antiseptic composition. The amount of humectant may vary outside ofthe ranges above, but is typically both whole and fractional valueswithin these ranges. Further, it is to be appreciated that more than onehumectant may be included in the antiseptic composition, in which casethe total amount of all the humectants included is within the aboveranges. For example, the humectant may comprise USP glycerol in anamount of from 2.0 to 3.0 wt. % based on the total weight of theantiseptic composition and propylene glycol in an amount of from 2.5 to3.5 wt. % based on the total weight of the antiseptic composition.

The antiseptic composition may further comprise an emollient. Theemollient may be of any type that is suitable for topical application toa patient. The emollient may be, by way of non-limiting example,petroleum-based oils, petrolatum, vegetable oils, mineral oils, lanolinand derivatives thereof, glycerol esters and derivatives thereof, fattyesters, propylene glycol esters and derivatives thereof, alkoxylatedcarboxylic acids, aloe vera, fatty alcohols, dimethicone, alkylmethicones, alkyl dimethicones, phenyl silcones, alkyl trimethylsilanes,and combinations thereof. In certain embodiments, the emollientcomprises dimethicone and aloe vera. Of course, still other emollientsare contemplated.

When present, the emollient or other components of the antisepticcomposition may comprise insoluble particles. In the context of thisdisclosure “insoluble particles” are particles that are not soluble inthe solvent of the antiseptic composition. In certain embodiments, theinsoluble particles have an average diameter of greater than 0.2 micronssuch that the antiseptic composition may not be sterilized by filtrationbecause the insoluble particles are too large.

When present, the emollient may be included in the antisepticcomposition in an amount less than 10 wt. % based on the total weight ofthe antiseptic composition. In another embodiment, the emollient may beincluded in the antiseptic composition an amount less than 5 wt. % basedon the total weight of the antiseptic composition. In other embodiments,the emollient is included in the antiseptic composition in an amountless than 2.5, less than 2.0, less than 1.5, less than 1.0, less than0.5, less than 0.25, or less than 0.2, wt. % based on the total weightof the antiseptic composition. Alternatively, the antiseptic compositioncomprises an amount of emollient of from 0.01 to 1, 0.1 to 0.25, or 0.1to 0.2, wt. % based on the total weight of the antiseptic composition.The amount of emollient may vary outside of the ranges above, but istypically both whole and fractional values within these ranges. Further,it is to be appreciated that more than one emollient may be included inthe antiseptic composition, in which case the total amount of all theemollients included is within the above ranges.

The antiseptic composition may further comprise a surfactant. Thesurfactant may be any surfactant that is compatible with theantibacterial agent of the antiseptic composition. Depending on theantibacterial agent included in the antiseptic composition, thesurfactant may be a cationic surfactant, an anionic surfactant,non-ionic surfactant, or combinations thereof. When the surfactant is anon-ionic surfactant, the non-ionic surfactant may be, by way ofnon-limiting example, polysorbate 20, polysorbate 40, polysorbate 60,polysorbate 80, polysorbate 120, a polyoxyethylene alkyl ether,polyoxyethylene cetyl ether, polyoxyethylene palmityl ether,polyoxyethylene oxide hexadecyl ether, polyethylene glycol cetyl ether,a sucrose ester, a partial ester of sorbitol, a monoglyceride, adiglyceride, di- and tri-esters of sucrose with fatty acid, nonylphenolethoxylate (Igepal CO 630), nonoxynol-9 and combinations thereof Incertain embodiments, the surfactant comprises polysorbate 20 and IgepalCO 630. Of course, still other surfactants are contemplated.

When present, the surfactant may be included in the antisepticcomposition in an amount less than 5.0 wt. % based on the total weightof the antiseptic composition. In another embodiment, the surfactant maybe included in the antiseptic composition in an amount less than 2.5 wt.% based on the total weight of the antiseptic composition. In otherembodiments, the surfactant may be included in the antisepticcomposition in an amount less than 2.0, less than 1.5, less than 1.0,less than 0.75, less than 0.50, less than 0.25, less than 0.2, less than0.15, or less than 0.1, wt. % based on the total weight of theantiseptic composition. Alternatively, the surfactant may be included inthe antiseptic composition in an amount of from 0.01 to 2, 0.05 to 1.5,or 0.01 to 0.75, wt. % based on the antiseptic composition. The amountof surfactant may vary outside of the ranges above, but is typicallyboth whole and fractional values within these ranges. Further, it is tobe appreciated that more than one surfactant may be included in theantiseptic composition, in which case the total amount of all thesurfactants included is within the above ranges.

The antiseptic composition may further comprise a pH adjuster. The pHadjuster may be any pH adjuster compatible for use in the antisepticcomposition. The pH adjuster may be, by way of non-limiting example,adipic acid and derivatives thereof, glycine and derivatives thereof,citric acid and derivatives thereof, calcium hydroxide, magnesiumaluminometasilicate, glucono delta lactone, or combinations thereof. Incertain embodiments, the pH adjuster is glucono delta lactone. Ofcourse, still other pH adjusters are contemplated.

When present, the pH adjuster may be included in the antisepticcomposition in an amount less than 5 wt. % based on the total weight ofthe antiseptic composition. In another embodiment, the pH adjuster maybe included in the antiseptic composition in an amount less than 2.5 wt.% based on the total weight of the antiseptic composition. In otherembodiments, the pH adjuster may be included in the antisepticcomposition in an amount less than 2.0, less than 1.5, less than 1.0,less than 0.75, less than 0.50, less than 0.25, less than 0.2, less than0.15, or less than 0.1, wt. % based on the total weight of theantiseptic composition. Alternatively, the pH adjuster may be includedin the antiseptic composition in an amount of from 0.01 to 2, 0.05 to1.5, or 0.05 to 0.5, wt. % based on the antiseptic composition. Theamount of pH adjuster may vary outside of the ranges above, but istypically both whole and fractional values within these ranges. Further,it is to be appreciated that more than one pH adjuster may be includedin the antiseptic composition, in which case the total amount of all thepH adjusters included is within the above ranges.

The antiseptic composition may have any pH suitable for the antisepticcomposition to be used to disinfect the skin or mucous membranes of apatient, particularly in view of the antibacterial agent included in theantiseptic composition. In one embodiment, the antiseptic compositionmay have a pH of from 4 to 6. In another other embodiment, theantiseptic composition may have a pH of from 4.2 to 5.2. In still otherembodiment, the antiseptic composition may have a pH of from 4 to 8, offrom 4 to 7, of from 4 to 6, or of from 4 to 5. The pH of the antisepticcomposition may vary outside of the ranges above in specificembodiments, but is typically both whole and fractional values withinthese ranges.

The antiseptic composition may further comprise an odorant. The odorantmay be any odorant suitable for use in the antiseptic composition. Theodorant may be, by way of non-limiting example, perfumes, fragrances,ethereal oils, essences, scents, and combinations thereof. Of course,still other odorants are contemplated.

When present, the odorant may be included in the antiseptic compositionin an amount less than 5 wt. % based on the total weight of theantiseptic composition. In another embodiment, the odorant may beincluded in the antiseptic composition in an amount less than 2.5 wt. %based on the total weight of the antiseptic composition. In otherembodiments, the odorant may be included in the antiseptic compositionin an amount less than 2.0, less than 1.5, less than 1.0, less than0.75, less than 0.50, less than 0.25, less than 0.2, less than 0.15, orless than 0.1, wt. % based on the total weight of the antisepticcomposition. Alternatively, the odorant may be included in theantiseptic composition in an amount of from 0.001 to 2, 0.005 to 1.5, or0.005 to 0.5, wt. % based on the antiseptic composition. The amount ofodorant may vary outside of the ranges above, but is typically bothwhole and fractional values within these ranges. Further, it is to beappreciated that more than one odorant may be included in the antisepticcomposition, in which case the total amount of all the odorants includedis within the above ranges.

The antiseptic composition may further comprise a colorant. The colorantmay be any colorant suitable for use in the antiseptic composition. Thecolorant may be a synthetically derived colorant or a naturally derivedcolorant. The colorant may be, by way of non-limiting example, BrilliantBlue FCF, Fast Green FCF, indigo carmine, carmoisine lake, erythrosine,carmine lake, tartrazine, annatto, colorants produced by converting anaturally derived colorant to an aluminum or calcium salt, andcombinations thereof. Of course, still other colorants are contemplated.

When present, the colorant may be included in the antiseptic compositionin an amount less than 5 wt. % based on the total weight of theantiseptic composition. In another embodiment, the colorant may beincluded in the antiseptic composition in an amount less than 2.5 wt. %based on the total weight of the antiseptic composition. In otherembodiments, the colorant may be included in the antiseptic compositionin an amount less than 2.0, less than 1.5, less than 1.0, less than0.75, less than 0.50, less than 0.25, less than 0.2, less than 0.15, orless than 0.1, wt. % based on the total weight of the antisepticcomposition. Alternatively, the colorant may be included in theantiseptic composition in an amount of from 0.001 to 2, 0.005 to 1.5, or0.005 to 0.5, wt. % based on the antiseptic composition. The amount ofcolorant may vary outside of the ranges above, but is typically bothwhole and fractional values within these ranges. Further, it is to beappreciated that more than one colorant may be included in theantiseptic composition, in which case the total amount of all thecolorants included is within the above ranges.

The antiseptic composition may further comprise a stabilizer, a skinprotectant, a preservative, or combinations thereof. When present, thestabilizer, the skin protectant, and/or the preservative may each beincluded in the antiseptic composition in amounts of less than 5 wt. %based on the total weight of the antiseptic composition. In anotherembodiment, the stabilizer, the skin protectant, and/or the preservativemay each be included in the antiseptic composition in an amount lessthan 2.5 wt. % based on the total weight of the antiseptic composition.In other embodiments, the stabilizer, the skin protectant, and/or thepreservative may be each included in the antiseptic composition in anamount less than 2.0, less than 1.5, less than 1.0, less than 0.75, lessthan 0.50, less than 0.25, less than 0.2, less than 0.15, or less than0.1, wt. % based on the total weight of the antiseptic composition.Alternatively, the stabilizer, the skin protectant, and/or thepreservative may each be included in the antiseptic composition in anamount of from 0.001 to 2, 0.01 to 1.5, or 0.01 to 0.5, wt. % based onthe antiseptic composition. The amount of the stabilizer, the skinprotectant, and/or the preservative may vary outside of the rangesabove, but is typically both whole and fractional values within theseranges. Further, it is to be appreciated that more than one of thestabilizer, the skin protectant, and/or the preservative may be includedin the antiseptic composition, in which case the total amount of all thestabilizers, the skin protectants, and/or the preservatives included iswithin the above ranges.

In one particular embodiment, the antiseptic composition includes lessthan 10, 5, 3, 1, 0.5, or 0.1, wt. % of an anionic compound. Forconfigurations where the antibacterial agent comprises CHG, anioniccompounds may compromise the efficacy of the antiseptic composition. Assuch, the selection of the components included in the antisepticcomposition may account for this characteristic. For example, inembodiments where the antiseptic composition includes at least one ofthe humectant, the emollient, the surfactant, the pH adjuster, theodorant, the colorant, the stabilizer, the preservative, and/or the skinprotectant, each of these components included may be non-ionic orcationic. In still further embodiments, the antiseptic composition maybe free of an anionic compound other than the anionic compound(s)included as the antibacterial agent. In other words, no anionic compoundmay be included in the antiseptic composition, other than those anioniccompounds of the antibacterial agent.

In some embodiments, the antiseptic composition is free of an alcoholhaving a boiling point less than 90° C. at 1.0 atm. By way ofnon-limiting example, an alcohol having a boiling point less than 90° C.at 1.0 atm may be ethanol or isopropyl alcohol. Alternatively, theantiseptic composition may include less than 5.0 wt. % alcohol having aboiling point less than 90° C. at 1.0 atm based on the total weight ofthe antiseptic composition. Alternatively still, the antisepticcomposition includes less than 4.0 wt. %, less than 3.0 wt. %, less than2.0 wt. %,or less than 1.0 wt. %, of alcohol having a boiling point lessthan 90° C. at 1.0 atm, each based on the total weight of the antisepticcomposition. In these embodiments, the antiseptic composition isparticularly suitable for disinfection of the skin or mucous membranesof a patient because the antiseptic composition does not dry the skin ormucous membranes of the patient. Moreover, the antiseptic compositionmay be applied to the skin or mucous membranes of a patient multipletimes within a 24 hour period without concern for irritating the skin ormucous membranes of the patient due to dryness. However, despite thefact that an alcohol having a boiling point less than 90° C. at 1.0 atmis generally not necessary, in certain embodiments, the antisepticcomposition may include an alcohol having a boiling point less than 90°C. at 1.0 atm in an amount of from 5 to 15 wt. % based on the totalweight of the antiseptic composition.

The antiseptic composition may include less than 10, less than 7.5, lessthan 5.0, less than 2.5, less than 1.0, or less than 0.5 wt. % of analcohol based on the total weight of the antiseptic composition wt. % ofan alcohol based on the total weight of the antiseptic composition.Alternatively, the antiseptic composition includes no amount of analcohol. In these embodiments, the antiseptic composition isparticularly suitable for disinfection of the skin or mucous membranesof a patient because the antiseptic composition does not dry the skin ormucous membranes of the patient. Of course, it will be appreciated thatin some embodiments, alcohol may be included in the antisepticcomposition in amounts greater than 10 wt. % based on the total weightof the antiseptic composition.

In some embodiments, the antiseptic composition is non-flammable. Theantiseptic composition may be non-flammable such that the flash point ofthe antiseptic composition is at least 38° C., at least 60° C., or atleast 93° C. In this manner, the antiseptic composition of thechlorhexidine article reduces the potential risk of fire that may beassociated with other antiseptic compositions such as those thatcontain, for example, ethanol or isopropyl alcohol.

In one particular embodiment, the antiseptic composition comprises waterin an amount of at least 50 wt. % based on the total weight of theantiseptic composition and chlorhexidine gluconate (CHG) in an amount offrom 1.5 to 5.0 wt. % based on the total weight of the antisepticcomposition. The CHG is dissolved in the water. In another embodiment,the antiseptic composition consists essentially of water in an amount ofat least 50 wt. % based on the total weight of the antisepticcomposition, chlorhexidine gluconate (CHG) in an amount of from 1.5 to5.0 wt. % based on the total weight of the antiseptic composition, ahumectant in an amount of from 3.0 to 10 wt. % based on the total weightof the antiseptic composition, an emollient in an amount less than 1.0wt. % based on the total weight of the antiseptic composition, andoptionally additives selected from the group consisting of a solvent, anantibacterial agent, a humectant, an emollient, a surfactant, a pHadjuster, an odorant, a colorant, or combinations thereof.

In various embodiments, the antiseptic composition is, comprises, orconsists essentially of an antibacterial agent and a solvent. Forexample, in embodiments that “consist essentially of” the aforementionedcomponents, the antiseptic composition may be free of the humectant, theemollient, the surfactant, the pH adjuster, the odorant, the colorant,the stabilizer, the skin protectant, the preservative, and/orcombinations thereof Alternatively, any one or more of these componentsmay be included in an amount less than 25, 20, 15, 10, 5, 4, 3, 2, 1,0.1, 0.05, 0.01, etc., wt. % or any range thereof, based on a totalweight of the antiseptic composition. In various non-limitingembodiments, all values and ranges of values between the aforementionedvalues are hereby expressly contemplated.

It should be appreciated that the ranges provided above for each of thecomponents of the antiseptic compositions may refer to the amounts ofthose components in the sterilized antiseptic compositions or theunsterilized antiseptic compositions. Because certain sterilizationprocesses may cause certain components to degrade, the amount of eachcomponent in the antiseptic composition may vary from the non-sterilecondition to the sterilized condition. As but one example, thedescription provided above should be understood to encompass thepossibility that the sterilized antiseptic composition may comprise anamount of from 0.1 to 5 wt. % of the antibacterial agent, oralternatively, that the unsterilized antiseptic composition may comprisean amount of from 0.1 to 5 wt. % of the antibacterial agent.

Referring again to FIG. 4, in certain embodiments, the antisepticcomposition is impregnated in the applicator 24. In some embodiments,when the antiseptic composition is impregnated in the applicator 24, theantiseptic composition may be dispersed evenly in the applicator 24 suchthat the concentration of the antiseptic composition is substantiallythe same (+/−1, 3, 5, or 10 wt. %) at all regions of the applicator 24.In other embodiments, the antiseptic composition may be impregnated inthe applicator 24 such that a region of the applicator 24 may have agreater concentration of the antiseptic composition than another region.By way of non-limiting example, the antiseptic composition may beimpregnated in the applicator 24 such that the concentration of theantiseptic composition is greater at a surface of the applicator 24 thanbeneath the surface of the applicator, or vice-versa.

As will be described in further detail below, in some embodiments, whenthe antiseptic composition is impregnated in the applicator 24, theantiseptic composition may be impregnated in the applicator 24 an amountof from 0.1 to 100 g per applicator. In another embodiment, theantiseptic composition may be impregnated in the applicator 24 in anamount of from 15 to 40 g per applicator. In other embodiments, theantiseptic composition may be impregnated in the applicator 24 in anamount of from 0.1 to 90, of from 0.1 to 80, of from 0.1 to 70, of from0.1 to 60, of from 0.1 to 50, of from 0.1 to 40, of from 0.1 to 30, offrom 0.1 to 20, of from 0.1 to 10, of from 0.1 to 5, or of from 0.1 to2.5, g. In still other embodiments, the antiseptic composition may beimpregnated in the applicator 24 in an amount of from 2.5 to 100, offrom 5 to 100, of from 10 to 100, of from 20 to 100, of from 30 to 100,of from 40 to 100, of from 50 to 100, of from 60 to 100, of from 70 to100, of from 80 to 100, of from 90 to 100, g. In still otherembodiments, the antiseptic composition may be impregnated in theapplicator 24 in an amount of from 5 to 50 g, of from 10 to 40, of from15 to 30, or of from 22.5 to 27.5, g.

In some embodiments, the antiseptic composition may be impregnated inthe applicator 24 in an amount of from 0.1 to 100 mL per applicator. Inanother embodiment, the antiseptic composition may be impregnated in theapplicator 24 in an amount of from 15 to 40 mL per applicator. In otherembodiments, the antiseptic composition may be impregnated in theapplicator 24 in an amount of from 0.1 to 90, of from 0.1 to 80, of from0.1 to 70, of from 0.1 to 60, of from 0.1 to 50, of from 0.1 to 40, offrom 0.1 to 30, of from 0.1 to 20, of from 0.1 to 10, of from 0.1 to 5,or of from 0.1 to 2.5, mL. In still other embodiments, the antisepticcomposition may be impregnated in the applicator 24 in an amount of from2.5 to 100, of from 5 to 100, of from 10 to 100, of from 20 to 100, offrom 30 to 100, of from 40 to 100, of from 50 to 100, of from 60 to 100,of from 70 to 100, of from 80 to 100, of from 90 to 100, mL. In stillother embodiments, the antiseptic composition may be impregnated in theapplicator 24 in an amount of from 5 to 50 g, of from 10 to 40, of from15 to 30, or of from 22.5 to 27.5, mL.

The antiseptic composition may be impregnated in the applicator 24 in anamount such that the concentration of the antibacterial agent istherapeutically effective in each applicator. In one embodiment, theantiseptic composition is impregnated in the applicator 24 such thatantibacterial agent is included in an amount of from 50 to 1000 mg perapplicator 24. In other embodiments, the antiseptic composition isimpregnated in the applicator 24 such that antibacterial agent isincluded in an amount of from 100 to 900, 200 to 800, 300 to 700, 400 to600, or 450 to 550, mg per applicator 24. In certain embodiments, whenCHG is the antibacterial agent, the antiseptic composition may beimpregnated in the applicator 24 such that CHG is included in an amountof from 400 to 600 mg per applicator 24.

In instances where the applicator is not impregnated, but ratherincludes a receptacle for retaining the antiseptic composition beforeactivation by the caregiver, each receptacle may comprise the antisepticcomposition in an amount of from 0.1 to 100, 15 to 40, 0.1 to 90, 0.1 to80, 0.1 to 70, 0.1 to 60, 0.1 to 50, 0.1 to 40, 0.1 to 30, 0.1 to 20,0.1 to 10, 0.1 to 5, 0.1 to 2.5, g per receptacle. The antisepticcomposition may be included in the receptacle such that theantibacterial agent is included in an amount of from 100 to 900, 200 to800, 300 to 700, 400 to 600, or 450 to 550, mg per receptacle.

In some embodiments, the chlorhexidine product may further comprise aninsert. The insert may be disposed in the package to support thechlorhexidine article and insulate the chlorhexidine article. As anexample, the insert may insulate the chlorhexidine article disposed inthe package during heating of the chlorhexidine article prior toapplication of the chlorhexidine article to the skin or mucous membranesof a patient. Furthermore, the insert may be used to support theapplicator when the applicator is impregnated with the antisepticcomposition. In this manner, the insert may ensure the applicator doesnot become contaminated during impregnation of the antisepticcomposition.

As will be described below, the chlorhexidine article 14 undergoes asterilization process, such as a terminal sterilization process, to forma sterilized chlorhexidine article 14. The chlorhexidine article 14 maybe subjected to any sterilization process suitable to sterilize thechlorhexidine article 14 such that the sterility of the chlorhexidinearticle 14 can be validated. For example, the chlorhexidine article 14may be subjected to heat sterilization, radiation sterilization,ethylene oxide gas sterilization, or combinations thereof

In the context of this disclosure, when the chlorhexidine article 14 issterilized, the components of the chlorhexidine article 14 are in asterile condition, and that sterile condition has been validated, theresultant article is referred to as a sterilized chlorhexidine article14. Accordingly, when the chlorhexidine article 14 is in the sterilecondition, the applicator 24, the antiseptic composition, and componentsthereof, are referred to as a ‘sterilized’ applicator 24 and a‘sterilized’ antiseptic composition, etc.

The sterile condition of the chlorhexidine article 14, or componentsthereof, may be defined as sterile in accordance with one or more ISOstandards. By way of non-limiting example, the sterilized chlorhexidinearticle 14 may be sterile in accordance with ISO 20857, ISO 17665, ISO11135, and/or ISO 11137. In some embodiments, the sterilizedchlorhexidine article 14 may be sterile in accordance with ISO 11137.

When the chlorhexidine article 14, or components thereof, is exposed toa sterilization process, the sterilized chlorhexidine article 14, orcomponents thereof, has a Sterility Assurance Level (SAL) equal to orless than 10⁻³. In the context of this disclosure, “SAL” means theprobability of a chlorhexidine article 14 being in a non-sterilecondition after the chlorhexidine article 14 has been subjected to asterilization process (and remains in the package 12 free from furtherexternal contamination).

In one aspect, the sterilization process may be understood as a step orsequence of steps that are sufficient to give the chlorhexidine article14 a SAL equal to or less than 10⁻³. In certain embodiments, thesterilized chlorhexidine article 14 has a SAL equal to or less than10⁻⁶. In other embodiments, the sterilized chlorhexidine article 14 hasa SAL of from 10⁻³ to 10⁻¹², of from 10⁻³ to 10⁻⁹, or of from 10⁻³ to10′. In still other embodiments, the sterilized chlorhexidine article 14has a SAL of from 10⁻⁶ to 10⁻¹², or of from 10⁻⁹ to 10⁻¹². In stillother embodiments, the sterilized chlorhexidine article 14 has a SAL ofless than 10⁻⁹, or less than 10⁻¹². In some embodiments, thechlorhexidine article 14 has a SAL of from 10⁻³ to 10⁻⁹. As describedabove, the components of the sterilized chlorhexidine article 14 mayalso have a SAL corresponding to the SAL of the sterilized chlorhexidinearticle 14. For example, the sterilized water, the sterilized applicator24, and the other components of the sterilized article may have a SAL offrom 10⁻³ to 10⁻¹², of from 10⁻³ to 10⁻⁹, or of from 10⁻³ to 10⁻⁶.

In one embodiment, when the chlorhexidine product 10 is subjected to asterilization process, such as a terminal sterilization process, it willbe appreciated that the package 12 is also subjected to thesterilization process in addition to the chlorhexidine article 14disposed therein. However, as the external surface of the package 12 isexposed to the environment during subsequent handling(post-sterilizing), the external surface of the package 12 may notremain sterile even though the sterilized chlorhexidine article 14 doesremain in the sterile condition. Despite the fact that the externalsurface of the package 12 may not remain sterile, the interior volume 16of the package 12 remains sterile at least until the package 12 isopened. In the context of this disclosure, the term package 12 is usedto refer to both a sterilized package 12 and a non-sterilized package12.

When the chlorhexidine article is sterilized, the sterilized antisepticcomposition may further comprise degradation impurities. The degradationimpurities may be a result of exposing the chlorhexidine article to thesterilization process. When the sterilization process is heatsterilization, or radiation sterilization, and the antibacterial agentcomprises CHG, the degradation impurities may include, by way ofnon-limiting example,N-[[6-[[[(4-chlorophenyl)carbamimidoyl]carbamimidoyl]-amino]hexyl]carbamimidoyl]urea,N-(4-chlorophenyl)guanidine, N-(4-chlorophenyl)urea,1-(6-aminohexyl)-5-(4-chlorophenyl)biguanide,N-(4-chlorophenyl)-N′-[[6-[[[(4-chlorophenyl)carbamimidoyl]carbamimidoyl]amino]hexyl]carbamimidoyl]urea,1-(4-chlorophenyl)-5-[6-[[(phenylcarbamimidoyl)carbamimidoyl]amino]hexyl]biguanide,1-[6-(carbamimidoylamino)hexyl]-5-(4-chlorophenyl)-biguanide,p-chloroaniline, and combinations thereof. Of course still otherdegradation impurities of CHG are contemplated. Furthermore, degradationimpurities for antibacterial agents other than CHG are alsocontemplated.

In one embodiment, the sterilized antiseptic composition is free fromdegradation impurities with a concentration having a toxicityunacceptable for topical skin applications according to ICH Q3. In oneaspect, the sterilized antiseptic composition comprises less than 1,less than 0.1, less than 0.01, or less than 0.001 of a toxic degradationimpurity.

When present, the degradation impurities may be included in thesterilized antiseptic composition in an amount less than 2.0 wt. % basedon the total weight of the sterilized antiseptic composition. In anotherembodiment, the degradation impurities may be included in the sterilizedantiseptic composition in an amount less than 5.0 wt. % based on thetotal weight of the sterilized antiseptic composition. In otherembodiments, the degradation impurities may be included in thesterilized antiseptic composition in an amount less than 1.75, less than1.5, less than 1.25, less than, 1.0, less than, 0.75, less than 0.5,less than 0.25, less than 0.2, less than 0.1, less than 0.05, less than0.01, or less than 0.001 wt. % based on the total weight of thesterilized antiseptic composition. In still other embodiments, thedegradation impurities may be included in the sterilized antisepticcomposition in an amount of from 0.001 to 0.01, of from 0.001 to 0.1, offrom 0.001 to 0.2, of from 0.001 to 0.25, of from 0.001 to 0.5, of from0.001 to 0.75, of from 0.001 to 1.0, of from 0.001 to 1.25, of from0.001 to 1.5, of from 0.001 to 1.75, or of from 0.001 to 2.0, wt. %based on the total weight of the sterilized antiseptic composition. Theamount of degradation impurities may vary outside of the ranges above,but is typically both whole and fractional values within these ranges.Further, it is to be appreciated that more than one degradation impuritymay be included in the antiseptic composition, in which case the totalamount of all the degradation impurities included is within the aboveranges.

The present disclosure also provides a method of sterilizing achlorhexidine article.

The method of sterilizing the chlorhexidine article 14 comprisesproviding the applicator and providing the antiseptic composition. Insome embodiments, providing the antiseptic composition may furthercomprise providing the solvent, providing the antibacterial agent, andcombining the solvent and the antibacterial agent to form the antisepticcomposition. In other embodiments, providing the antiseptic compositionmay further comprise providing the solvent, providing the antibacterialagent, providing at least one of the humectant, the emollient, thesurfactant, the pH adjuster, the odorant, the colorant, the stabilizer,the skin protectant, or the preservative, and combining the solvent, theantibacterial agent, and the at least one of the humectant, theemollient, the surfactant, the pH adjuster, the odorant, the colorant,the stabilizer, the skin protectant, or the preservative, to form theantiseptic composition. It is contemplated that when at least one of thehumectant, the emollient, the surfactant, the pH adjuster, the odorant,the colorant, the stabilizer, the skin protectant, or the preservativeis provided, the solvent and the at least one of the humectant, theemollient, the surfactant, the pH adjuster, the odorant, the colorant,the stabilizer, the skin protectant, or the preservative may be combinedfirst followed by combining the antibacterial agent, or in any othersuitable order of addition. In some embodiments, the antibacterial agentmay be combined with a portion of the solvent to form an antibacterialagent concentrate. By way of non-limiting example, the antibacterialagent concentrate may be 20 wt. % CHG dissolved in water. When theantibacterial agent concentrate is formed, the antibacterial agentconcentrate may be combined with the solvent, or the solvent and atleast one of the humectant, the emollient, the surfactant, the pHadjuster, the odorant, the colorant, the stabilizer, the skinprotectant, or the preservative, to form the antiseptic composition.

The method may further comprise impregnating the antiseptic compositionin the applicator 24 to form the chlorhexidine article 14. Theantiseptic composition may be impregnated in the applicator 24 in anyamount described herein to form the chlorhexidine article 14.Impregnating may be performed by spraying the antiseptic composition onthe applicator on one or multiple sides. The amount of antisepticcomposition that is impregnated may be appropriately metered to ensurethat the proper amount is provided in each applicator. As describedabove, the applicator 24 may be support by an insert during impregnationto ensure applicator does not become contaminated during impregnation.Alternatively, when the applicator comprises the receptacle forreceiving the antiseptic composition, the method of sterilizing thechlorhexidine article may comprise filling the receptacle of theapplicator with the antiseptic composition to form the chlorhexidinearticle.

Once the antiseptic composition has been impregnated in the applicator24, the chlorhexidine article 14 can be encompassed in the package 12.In one possible embodiment, the package 12 is wrapped around thechlorhexidine article 14 and prepared for sealing. However, it should beappreciated that other ways of encompassing the chlorhexidine article 14in the package 12 may also be used.

The method further comprises sealing the chlorhexidine article 14 insidethe package 12 to form the chlorhexidine product 10. The chlorhexidinearticle 14 may be sealed inside the package 12 such that thechlorhexidine article 14 is hermetically sealed inside the package 12.The chlorhexidine article 14 may be sealed inside the package 12 in anysuitable manner such as, by way of non-limiting example, heat sealing.Of course, other methods of sealing the chlorhexidine article 14 insidethe package 12 are contemplated. In some embodiments, the method ofsterilizing the chlorhexidine article 14 may further comprise disposingthe chlorhexidine article 14 within the interior volume 16 of thepackage 12 prior to sealing the chlorhexidine article 14 inside thepackage 12. In other embodiments, the method of sterilizing thechlorhexidine article 14 may further comprise disposing the package 12about the chlorhexidine article 14 prior to sealing the chlorhexidinearticle 14 inside the package 12. In another embodiment, sealing thechlorhexidine article 14 inside the package 12 may comprise shrinkwrapping the chlorhexidine article 14.

The method may further comprise cooling the chlorhexidine product 10.Because the chlorhexidine article 14 is disposed within the interiorvolume 16 of the package 12 at this point, the step of cooling may befurther understood to include the step of cooling the chlorhexidinearticle 14 and components thereof, including but not limited to, thesolvent, the antibacterial agent, etc. Cooling the chlorhexidine product10 may further comprise cooling the chlorhexidine product 10 such thatat least a portion of the solvent of the antiseptic compositionundergoes a phase change from a liquid state to a solid state.

Cooling the chlorhexidine product 10 may comprise cooling thechlorhexidine product 10 to a temperature of from −100° C. to 20° C. Inone embodiment, the chlorhexidine product 10 may be cooled to atemperature of from −30° C. to 3° C. In another embodiment, thechlorhexidine product 10 may be cooled to a temperature of from −80° C.to 5° C. In other embodiments, the chlorhexidine product 10 may becooled to a temperature of from −90° C. to 20° C., of from −80° C. to20° C., of from −70° C. to 20° C., of from −60° C. to 20° C., of from−50° C. to 20° C., of from −40° C. to 20° C., or of from −30° C. to 20°C. In certain embodiments, the chlorhexidine product 10 may be cooled toa temperature equal to or less than the freezing point of the solvent inthe antiseptic composition. By way of non-limiting example, if thesolvent comprises water, the chlorhexidine product 10 may be cooled to atemperature equal to or less than 0° C. Other suitable solvents andmelting points are contemplated such as, by way of non-limiting example,ethanol (−114° C.), or isopropyl alcohol (−89° C.). When the solventcomprises more than one solvent, the chlorhexidine product 10 may becooled to a temperature equal to or less than the melting point of theone of the solvents in the antiseptic composition. In still otherembodiments, the chlorhexidine product 10 may be cooled to a temperatureof from −40° C. to 10° C., of from −35° C. to 5° C., of from −30° C. to0° C., or of from −25° C. to 10° C. In still other embodiments, thechlorhexidine product 10 may be cooled to a temperature of from −40° C.to 5° C., of from −40° C. to 0° C., of from −40° C. to −5° C., of from−40° C. to −10° C., of from −40° C. to −15° C., or of from −25° C. to−15° C. Of course, still other temperatures are contemplated.

In one aspect, cooling the chlorhexidine product 10 may comprise coolingthe chlorhexidine product 10 such that at least 50 wt. % of the solventof the antiseptic composition undergoes a phase change from a liquidstate to a solid state. In another embodiment, cooling the chlorhexidineproduct 10 may comprise cooling the chlorhexidine product 10 such thatat least 0.1 wt. % of the solvent of the antiseptic compositionundergoes a phase change from a liquid state to a solid state. In otherembodiments, cooling the chlorhexidine product 10 may comprise coolingthe chlorhexidine product 10 such that at least 1, at least 5, at least10, at least 15, at least 20, at least 30, at least 40, at least 50, atleast 60, at least 70, at least 80, at least 90, at least 95, or atleast 99, wt. % of the solvent undergoes a phase change from a liquidstate to a solid state. In certain embodiments, cooling thechlorhexidine product 10 may comprise cooling the chlorhexidine product10 such that all of the solvent undergoes a phase change from a liquidstate to a solid state. Alternatively, cooling the chlorhexidine product10 may comprise cooling the chlorhexidine product 10 such that none ofthe solvent undergoes a phase change from a liquid state to a solidstate. In still other embodiments, cooling the chlorhexidine product 10may comprise cooling the chlorhexidine product 10 such that less than99, less than 95, less than 90, less than 80, less than 70, less than60, less than 50, less than 40, less than 30, less than 20, less than10, less than 5, or less than 1, wt. % of the solvent undergoes a phasechange from a liquid state to a solid state.

The cooling of the chlorhexidine product 10 may be performed atatmospheric pressure. By way of non-limiting example, the cooling of thechlorhexidine product 10 may be performed at a pressure of at least 1atm. In other embodiments, the cooling of the chlorhexidine product 10may be performed at a pressure of from 0.8 to 1.2, of from 0.9 to 1.1,or of from 0.95 to 1.05, atm. Furthermore, once the cooling of thechlorhexidine product 10 is complete the chlorhexidine product 10 maynot be exposed to pressures below atmospheric pressure. By way ofnon-limiting example, after cooling the chlorhexidine product 10 thechlorhexidine product 10 may not be exposed to pressures less than 0.95,less than 0.9, less than 0.8, or less than 0.5, atm. In this manner, thechlorhexidine product 10 is not subjected to lyophilization (also knownas freeze-drying).

With continued respect to cooling the chlorhexidine product 10, when aplurality of chlorhexidine articles 14 are included in the package 12,cooling the chlorhexidine product 10 may further comprise cooling thechlorhexidine product 10 such that at least a portion of the solvent inthe antiseptic composition of each chlorhexidine article 14 undergoes aphase change from a liquid state to a solid state. In anotherembodiment, when a plurality of chlorhexidine products 10 are disposedin the shipping container 22, cooling the chlorhexidine product 10 mayfurther comprise cooling the shipping container 22 such that at least aportion of the solvent in the antiseptic composition of eachchlorhexidine article 14 in each package 12 undergoes a phase changefrom a liquid state to a solid state.

With continued respect to cooling the chlorhexidine product 10, thechlorhexidine product 10 may be cooled by any suitable cooling unit 26.By way of non-limiting example, the cooling unit 26 may be a freezer, arefrigerator, a walk-in freezer, a walk-in cooler, a tunnel blastfreezer, or a refrigerated warehouse. Alternatively, the cooling unit 26may dispense liquid refrigerant such as by way of non-limiting example,liquid nitrogen, liquid nitrous oxide, or liquid carbon dioxide. Withreference to FIG. 7A, in one embodiment, the cooling unit 26 is a tunnelblast freezer 26. The tunnel blast freezer 26 may be arranged about aconveyor mechanism 28 to facilitate efficient cooling of the shippingcontainer 22 and the plurality of chlorhexidine products 10 disposedtherein. Likewise, as shown in FIG. 7B, the conveyor mechanism may beused to efficiently cool single chlorhexidine products 10 instead of theplurality of chlorhexidine products 10 disposed in the shippingcontainer 22. In other embodiments, a plurality of shipping containersand the chlorhexidine products 10 disposed therein may be cooled in afreezer, or a walk-in freezer.

The method further comprises sterilizing the chlorhexidine product 10 toform the sterilized chlorhexidine article 14. The chlorhexidine product10 may be sterilized by any sterilization process such that thesterility of the chlorhexidine article 14 can be verified. In someembodiments, sterilizing the chlorhexidine product 10 comprisesirradiating the chlorhexidine product 10 to form a sterilizedchlorhexidine article 14.

In other embodiments, sterilizing the chlorhexidine product 10 furthercomprises heat sterilizing the chlorhexidine product 10. Of course itshould be appreciated that the antibacterial agent of the antisepticcomposition may not be compatible with heat sterilization. For example,heat sterilization is known to be unsuitable for antiseptic compositionscomprising CHG in an amount of greater than 1.0 wt. % based on the totalweight of the antiseptic composition because of the degradation of CHGat temperatures required for heat sterilizing. Heat sterilizing may alsobe incompatible with the applicator 24 and/or package 12 of thechlorhexidine product 10.

In certain embodiments, depending on the chosen antibacterial agent, themethod may be free of a heating step that results in the temperature ofthe chlorhexidine article 14 being raised above 35, 40, 50, 60, or 70°C. In other embodiments, the method may be free of a heating step thatresults in the temperature of the chlorhexidine article 14 being raisedabove 30° C. In still other embodiments, the method may be free of aheating step that results in the temperature of the chlorhexidinearticle 14 to be raised such that the chlorhexidine article 14 isconsidered sterile in accordance with ISO 20857, or ISO 17665. In stillother embodiments, the method may be free of a heating step that resultsin the temperature of the chlorhexidine article 14 being raised to atemperature of from 35 to 150, of from 50 to 150, of from 50 to 130, orof from 75 to 130° C.

When the method comprises irradiating the chlorhexidine product 10 toform the sterilized chlorhexidine article 14, irradiating thechlorhexidine product 10 may comprise irradiating the chlorhexidineproduct 10 with a radiation type selected from the group comprisinggamma radiation, electron-beam radiation, x-ray radiation, orcombinations thereof. In certain embodiments, the radiation type iselectron-beam radiation.

The chlorhexidine product 10 may be irradiated with the radiation typeby any suitable radiation unit. With reference to FIGS. 7A and 7B, inthe illustrated embodiment, the radiation unit 30 is an irradiator 30.The radiation unit 30 may be arranged in any suitable manner toefficiently irradiate the chlorhexidine product 10. As an example, inthe illustrated embodiments, the irradiator 30 is disposed adjacent theconveyor mechanism 28 such that either of the chlorhexidine product 10,or the plurality of chlorhexidine products 10 disposed in the shippingcontainer 22, may be efficiently irradiated. With reference to FIG. 7A,the radiation unit 30 may be disposed adjacent the conveyor mechanism 28downstream of the cooling unit 26 for efficiently cooling the pluralityof chlorhexidine products 10 disposed in the shipping container 22 andsubsequently irradiating the plurality of chlorhexidine products 10disposed in the shipping container 22. Likewise, as shown in FIG. 7B,the conveyor mechanism 28 may also be used for efficiently cooling andirradiating only a single chlorhexidine product 10. It will further beappreciated that in some embodiments, the plurality of chlorhexidineproducts 10 may be irradiated simultaneously and not disposed in theshipping container 22. Of course, it will be appreciated that coolingthe chlorhexidine product 10 may occur separately from irradiating thechlorhexidine product 10. In some embodiments, the irradiator 30 may bearranged about an irradiation platform such that chlorhexidine productscan be placed on the irradiation platform and irradiated. Of courseother arrangements of the irradiator 30 are contemplated.

When the radiation unit 30 is the irradiator 30, the irradiator 30 maybe, by way of non-limiting example, an x-ray generator, a gamma rayirradiator, an electron-beam accelerator, or combinations thereof. Ofcourse, still other irradiators 30 are contemplated.

In some embodiments, when the chlorhexidine product 10 is irradiatedwith a radiation type, irradiating the chlorhexidine product 10 mayfurther comprise irradiating the chlorhexidine product 10 with aradiation dose of from 5 to 25 kGy to form the sterilized chlorhexidinearticle 14. In another embodiment, irradiating the chlorhexidine product10 may further comprise irradiating the chlorhexidine product 10 with aradiation dose of from 1 to 100 kGy. In another embodiment, irradiatingthe chlorhexidine product 10 may further comprise irradiating thechlorhexidine product 10 with a radiation dose of from 1 to 30 kGy. Inother embodiments, irradiating the chlorhexidine product 10 may furthercomprise irradiating the chlorhexidine product 10 with a radiation doseof from 1 to 55, of from 5 to 30, of from 10 to 25, or of from 10 to 20,of from 8 to 12, or of from 9 to 13, kGy. In still other embodiments,irradiating the chlorhexidine product 10 may further compriseirradiating the chlorhexidine product 10 with a radiation dose of atleast 1, at least 5, at least 10, at least 15, at least 20, at least 25,at least 30, at least 50, or at least 100, kGy. In still otherembodiments, irradiating the chlorhexidine product 10 may furthercomprise irradiating the chlorhexidine product 10 with a radiation doseof less than 100, less than 50, less than 30, less than 25, less than20, less than 15, less than 10, less than 5, or less than 1, kGy. Instill other embodiments, irradiating the chlorhexidine product 10 mayfurther comprise irradiating the chlorhexidine product 10 with aradiation dose of 5, 10, 15, 20, 25, or 30, kGy. Of course, still otherradiation doses are contemplated.

Irradiating the chlorhexidine product 10 may further compriseirradiating the chlorhexidine product 10 with a plurality of radiationdoses. The plurality of radiation doses may be any number of radiationdoses suitable to sterilize the chlorhexidine product 10. By way ofnon-limiting example, the plurality of doses may be of from 2 to 5, offrom 2 to 4, or of from 2 to 3, radiation doses. The chlorhexidineproduct 10 may be subjected to the plurality of radiation doses within7, within 6, within 5, within 3, within 3, within 2, or within 1, days.In other embodiments, the chlorhexidine product 10 may be subjected tothe plurality of radiation doses within 20, within 15, within 10, orwithin 5, hours. In one embodiment, the chlorhexidine product 10 may besubjected to one of the plurality of radiation doses immediately afteranother of the plurality of radiation doses. Each of the plurality ofradiation doses may be a radiation dose of from 5 to 25 kGy, or any ofthe radiation dose ranges described herein.

With continued respect to irradiating the chlorhexidine product 10,irradiating the chlorhexidine product 10 may further compriseirradiating the chlorhexidine product 10 while at least a portion of thesolvent is in the solid state to form the sterilized chlorhexidinearticle 14. In some embodiments, irradiating the chlorhexidine product10 may further comprise irradiating the chlorhexidine product 10 whileat least 50 wt. % of the solvent is in the solid state. In anotherembodiment, irradiating the chlorhexidine product 10 may furthercomprise irradiating the chlorhexidine product 10 while at least 75 wt.% of the solvent is in the solid state. In other embodiments,irradiating the chlorhexidine product 10 may further compriseirradiating the chlorhexidine product 10 while at least 1, at least 5,at least 10, at least 15, at least 20, at least 30, at least 40, atleast 60, at least 70, at least 80, at least 90, at least 95, or atleast 99, wt. % of the solvent is in the solid state. In certainembodiments, irradiating the chlorhexidine product 10 may furthercomprise irradiating the chlorhexidine product 10 while all of thesolvent is in the solid state. Alternatively, irradiating thechlorhexidine product 10 may further comprise irradiating thechlorhexidine product 10 while none of the solvent is in the solid stateirradiating the chlorhexidine product 10 may further compriseirradiating the chlorhexidine product 10 while less than 99, less than95, less than 90, less than 80, less than 70, less than 60, less than50, less than 40, less than 30, less than 20, less than 10, less than 5,or less than 1, wt. % of the solvent is in the solid state.

In some embodiments, the amount of solvent in the solid state when thechlorhexidine product 10 is irradiated is the same as the amount ofsolvent that undergoes a phase change from the liquid state to the solidstate when the chlorhexidine product 10 is cooled. For example, withreference to FIGS. 7A and 7B, when the radiation unit 30 is arrangeddownstream of the cooling unit 26 on the conveyor mechanism 28, theamount of solvent in the solid state when the chlorhexidine products areirradiated is the same, substantially the same, or slightly less than,the amount of solvent that undergoes a phase change from the liquidstate to the solid state during cooling of the chlorhexidine products10. Alternatively, the radiation unit may be arranged separately fromthe cooling unit. When the radiation unit is arranged separately fromthe cooling unit, the radiation unit may be arranged in a cooledenvironment to ensure the amount of solvent in the solid state when thechlorhexidine products 10 are irradiated is the same, substantially thesame, or slightly less than, the amount of solvent that undergoes aphase change from the liquid state to the solid state during cooling ofthe chlorhexidine products 10. Of course, the radiation unit may bearranged in a room temperature environment.

In other embodiments, the amount of solvent in the solid state when thechlorhexidine product 10 is irradiated is different to the amount ofsolvent that undergoes a phase change from the liquid state to the solidstate when the chlorhexidine product 10 is cooled.

In some embodiments, the sterilized antibacterial agent in thesterilized antiseptic composition has a purity of at least 90% afterirradiating the chlorhexidine product 10 to form the sterilizedchlorhexidine article 14. In the context of this disclosure, the purityof the sterilized antibacterial agent is the amount of sterilizedantibacterial agent in the sterilized antiseptic composition aftersterilizing the chlorhexidine product 10 divided by the sum of theamount of sterilized antibacterial agent and degradation impurities inthe sterilized antiseptic composition after sterilizing thechlorhexidine product 10, expressed as a percentage. The purity may beexpressed in the following formula:

${purity} = {\frac{\begin{matrix}{{amount}\mspace{14mu} {of}\mspace{14mu} {sterilized}\mspace{14mu} {antibacterial}\mspace{14mu} {agent}\mspace{14mu} {in}} \\{{the}\mspace{14mu} {sterilized}\mspace{14mu} {antiseptic}\mspace{14mu} {composition}}\end{matrix}}{\begin{pmatrix}\begin{matrix}{{amount}\mspace{14mu} {of}\mspace{14mu} {sterilized}\mspace{14mu} {antibacterial}\mspace{14mu} {agent}\mspace{14mu} {in}} \\{{{the}\mspace{14mu} {sterilized}\mspace{14mu} {antiseptic}\mspace{14mu} {composition}} +}\end{matrix} \\\begin{matrix}{{amount}\mspace{14mu} {of}\mspace{14mu} {degradation}\mspace{14mu} {impurities}\mspace{14mu} {in}\mspace{14mu} {the}} \\{{sterilized}\mspace{14mu} {antiseptic}\mspace{14mu} {composition}}\end{matrix}\end{pmatrix}} \times 100.}$

For example, a purity of 98% indicates that the sterilized antisepticcomposition comprises 98 parts of the sterilized antibacterial agent inthe sterilized antiseptic composition and 2 parts of the degradationimpurities in the sterilized antiseptic composition. In anotherembodiment, the sterilized antibacterial agent in the sterilizedantiseptic composition has a purity of at least 50%. In otherembodiments, the sterilized antibacterial agent in the sterilizedantiseptic composition has a purity of at least 60%, of at least 70%, ofat least 80%, of at least 90%, of at least 92.5%, of at least 95%, of atleast 97.5%, of at least 99%, of at least 99.5%, or of at least 99.9%.In certain embodiments, the sterilized antibacterial agent in thesterilized antiseptic composition has a purity of 100%. In other words,the sterilized antiseptic composition does not comprise any degradationimpurities. In still other embodiments, the sterilized antibacterialagent in the antiseptic composition has purity of from 85 to 99.5%, offrom 87.5 to 99.5%, or of from 87.5 to 97.5%. Of course, still otherpurities of the sterilized antibacterial agent of the sterilizedantiseptic composition are contemplated.

In some embodiments, the sterilized antibacterial agent in thesterilized antiseptic composition is present in an amount at least 90%of the amount of the antibacterial agent in the antiseptic compositionbefore sterilizing the chlorhexidine product 10. In another embodiment,the sterilized antibacterial agent in the sterilized antisepticcomposition is present in an amount at least 85% of the amount of theantibacterial agent in the antiseptic composition before sterilizing thechlorhexidine product 10. In still other embodiments, the sterilizedantibacterial agent in the sterilized antiseptic composition is presentin an amount at least 50%, at least 60%, at least 70%, at least 80%, atleast 92.5%, at least 95%, at least 97.5%, at least 99%, at least 99.5%,at least 99.9%, of the amount of the antibacterial agent in theantiseptic composition before sterilizing the chlorhexidine product 10.In certain embodiments, the sterilized antibacterial agent in thesterilized antiseptic composition is present in an amount equal to theamount of the antibacterial agent in the antiseptic composition beforesterilizing the chlorhexidine product 10. In still other embodiments,the sterilized antibacterial agent in the sterilized antisepticcomposition is present in an amount of from 85 to 99.5%, of from 87.5 to99.5%, or of from 87.5 to 97.5%, of the antibacterial agent in theantiseptic composition before sterilizing the chlorhexidine product 10.Of course, it is contemplated the sterilized antibacterial agent in thesterilized antiseptic composition is present in still other amounts.

In some embodiments, the antibacterial agent may be included in theantiseptic composition in an amount greater than the desired amount ofthe sterilized antibacterial agent in the sterilized antisepticcomposition. In this manner, if the amount of antibacterial agentdecreases during sterilization, there may still be a therapeuticallyeffective amount of the sterilized antibacterial agent included in thesterilized antiseptic composition. In one embodiment, the antibacterialagent may be included in an amount less than 35% greater than thedesired amount of the sterilized antibacterial agent included in thesterilized antiseptic composition. In another embodiment, theantibacterial agent may be included in the antiseptic composition anamount of from 15 to 25% greater than the desired amount of thesterilized antibacterial agent included in the sterilized antisepticcomposition. In still other embodiments, the antibacterial agent may beincluded in the antiseptic composition an amount less than 5%, less than10%, less than 15%, less than 20%, less than 25%, less than 30%, lessthan 40%, less than 50%, less than 60%, less than 70%, less than 80%,less than 90%, less than 100%, less than 200%, or less than 500%,greater than the desired amount of the sterilized antibacterial agentincluded in the sterilized antiseptic composition. In still otherembodiments, the antibacterial agent may be included in the antisepticcomposition an amount more than 5%, more than 10%, more than 15%, morethan 20%, more than 25%, more than 30%, more than 40%, more than 50%,more than 60%, more than 70%, more than 80%, more than 90%, more than100%, more than 200%, or more than 500%, greater than the desired amountof the sterilized antibacterial agent included in the sterilizedantiseptic composition. Of course, the antibacterial agent may beincluded in the antiseptic composition in still other amounts greaterthan the desired amount of the sterilized antibacterial agent in thesterilized antiseptic composition.

When the antibacterial agent is included in the antiseptic compositionamounts greater than the desired amount of the sterilized antibacterialagent in the sterilized antiseptic composition, the sterilizedantibacterial agent may be included in the sterilized antisepticcomposition in an amount of from 0.1 to 10 wt. % based on the totalweight of the sterilized antiseptic composition. In another embodiment,the sterilized antibacterial agent may be included in an amount of from1.5 to 5.0 wt. % based on the total weight of the sterilized antisepticcomposition. In other embodiments, the sterilized antibacterial agentmay be included in an amount from 0.5 to 10, of from 1.0 to 10, of from1.5 to 10, of from 2.0, to 10, of from 2.5 to 10, of from 3.0 to 10, offrom 3.5 to 10, of from 4.0 to 10, of from 4.5 to 10, of from 5.0 to 10,of from 5.5 to 10, of from 6.0 to 10, of from 6.5 to 10, of from 7.0 to10, of from 7.5 to 10, of from 8.0 to 10, of from 8.5 to 10, of from 9.0to 10, or of from 9.5 to 10 wt. % based on the total weight of thesterilized antiseptic composition. In still other embodiments, thesterilized antibacterial agent may be included in the sterilizedantiseptic composition in an amount of from 0.1 to 9.5, of from 0.1 to9.0, of from 0.1 to 8.5, of from 0.1 to 8.0, of from 0.1 to 7.5, of from0.1 to 7.0, of from 0.1 to 6.5, of from 0.1 to 6.0, of from 0.1 to 5.5,of from 0.1 to 5.0, of from 0.1 to 4.5, of from 0.1 to 4.0, of from 0.1to 3.5, of from 0.1 to 3.0, of from 0.1 to 2.5, of from 0.1 to 2.0, offrom 0.1 to 1.5, of from 0.1 to 1.0, or of from 0.1 to 0.5, wt. % basedon the total weight of the sterilized antiseptic composition. In stillother embodiments, the sterilized antibacterial agent may be included inthe sterilized antiseptic composition in an amount of from 0.5 to 8.0,of from 1.0 to 6.0, of from 1.5 to 5.0, of from 1.8 to 4.5, of from 1.8to 3.5, or of from 1.8 to 2.5, wt. % based on the total weight of thesterilized antiseptic composition. Of course, the sterilizedantibacterial agent may be included in the sterilized antisepticcomposition in still other amounts.

In one embodiment, the method of sterilizing a chlorhexidine articlecomprises providing an applicator. The method further comprises,providing an antiseptic composition comprising water in an amount offrom 50 wt. % based on the total weight of the antiseptic compositionand CHG in an amount of from 1.5 to 5.0 wt. % based on the total weightof the antiseptic composition. The method further comprises,impregnating the antiseptic composition in the applicator to form thechlorhexidine article. The method further comprises sealing thechlorhexidine article inside the package to form the chlorhexidineproduct. The method further comprises cooling the chlorhexidine productsuch that at least a portion of the water of the antiseptic compositionundergoes a phase change from the liquid state to the solid state. Themethod further comprises irradiating the chlorhexidine product while atleast a portion of the water is in the solid state to form thesterilized chlorhexidine article.

In another embodiment, the method of sterilizing a chlorhexidine articlecomprises providing the chlorhexidine product. The method also comprisescooling the chlorhexidine product such that at a least a portion of thesolvent of the antiseptic composition undergoes a phase change from aliquid state to a solid state. The method further comprises irradiatingthe chlorhexidine product while at least a portion of the solvent is inthe solid state to form a sterilized chlorhexidine article.

One or more of the values described above may vary by ±5%, ±10%, ±15%,±20%, ±25%, etc. so long as the variance remains within the scope of thedisclosure. Each member may be relied upon individually and or incombination and provides adequate support for specific embodimentswithin the scope of the appended claims. The subject matter of allcombinations of independent and dependent claims, both singly andmultiply dependent, is herein expressly contemplated. The disclosure isillustrative including words of description rather than of limitation.Many modifications and variations of the present disclosure are possiblein light of the above teachings, and the disclosure may be practicedotherwise than as specifically described herein.

All combinations of the aforementioned embodiments throughout the entiredisclosure are hereby expressly contemplated in one or more non-limitingembodiments even if such a disclosure is not described verbatim in asingle paragraph or section above. In other words, an expresslycontemplated embodiment may include any one or more elements describedabove selected and combined from any portion of the disclosure

It is also to be understood that any ranges and subranges relied upon indescribing various embodiments of the present disclosure independentlyand collectively fall within the scope of the appended claims, and areunderstood to describe and contemplate all ranges including whole and/orfractional values therein, even if such values are not expressly writtenherein. One of skill in the art readily recognizes that the enumeratedranges and subranges sufficiently describe and enable variousembodiments of the present disclosure, and such ranges and subranges maybe further delineated into relevant halves, thirds, quarters, fifths,and so on. As just one example, a range “of from 0.1 to 0.9” may befurther delineated into a lower third, i.e. from 0.1 to 0.3, a middlethird, i.e. from 0.4 to 0.6, and an upper third, i.e. from 0.7 to 0.9,which individually and collectively are within the scope of the appendedclaims, and may be relied upon individually and/or collectively andprovide adequate support for specific embodiments within the scope ofthe appended claims. In addition, with respect to the language whichdefines or modifies a range, such as “at least,” “greater than,” “lessthan,” “no more than,” and the like, it is to be understood that suchlanguage includes subranges and/or an upper or lower limit. As anotherexample, a range of “at least 10” inherently includes a subrange of fromat least 10 to 35, a subrange of from at least 10 to 25, a subrange offrom 25 to 35, and so on, and each subrange may be relied uponindividually and/or collectively and provides adequate support forspecific embodiments within the scope of the appended claims. Finally,an individual number within a disclosed range may be relied upon andprovides adequate support for specific embodiments within the scope ofthe appended claims. For example, a range “of from 1 to 9” includesvarious individual integers, such as 3, as well as individual numbersincluding a decimal point (or fraction), such as 4.1, which may berelied upon and provide adequate support for specific embodiments withinthe scope of the appended claims.

Several embodiments have been discussed in the foregoing description.However, the embodiments discussed herein are not intended to beexhaustive or limit the invention to any particular form. Theterminology which has been used is intended to be in the nature of wordsof description rather than of limitation. Many modifications andvariations are possible in light of the above teachings and theinvention may be practiced otherwise than as specifically described.

What is claimed is:
 1. A sterilized chlorhexidine product for topicaldisinfection, comprising: a package; and at least one sterilizedchlorhexidine article comprising a cloth; wherein the package comprises:a film defining an interior volume, the sterilized chlorhexidine articledisposed within the interior volume; a first sealed end portionpositioned at a first end of the film; and a second sealed end portionpositioned at a second end of the film; wherein the first sealed endportion and the second sealed end portion define a hermetically sealedportion about the interior volume.
 2. The sterilized chlorhexidineproduct of claim 1, wherein the package further comprises a tear portionfor providing access to the interior volume, wherein the tear portion ofthe package is arranged on the first sealed end portion or the secondsealed end portion such that the hermetically sealed portion ismaintained.
 3. The sterilized chlorhexidine product of claim 1, furthercomprising: an outlet in the package defined by the film, the outletconfigured to dispense the chlorhexidine article; and a label applied tothe package to cover the outlet.
 4. The sterilized chlorhexidine productof claim 3, wherein the label further comprises a free end for peelingthe label to expose the outlet.
 5. The sterilized chlorhexidine productof claim 1, wherein the package comprises a rectangular geometry.
 6. Thesterilized chlorhexidine product of claim 1, further comprising apredetermined number of sterilized chlorhexidine articles, thepredetermined number of chlorhexidine articles corresponding to aparticular task.
 7. The sterilized chlorhexidine product of claim 6,comprising two sterilized chlorhexidine articles in the package.
 8. Thesterilized chlorhexidine product of claim 1, wherein the cloth comprisesa fiber, wherein the fiber is a synthetic fiber.
 9. The sterilizedchlorhexidine product of claim 8, wherein the fiber comprises one ormore of a polyester fiber, a polypropylene fiber, a polyethylene fiber,a rayon fiber, a nylon fiber, an acrylic fiber, an acetate fiber, aspandex fiber, a latex fiber, and a Kevlar fiber.
 10. The sterilizedchlorhexidine product of claim 1, wherein the sterilized chlorhexidinearticle comprises an antiseptic composition.
 11. The sterilizedchlorhexidine product of claim 10, wherein antiseptic compositionremains in the sterilized chlorhexidine article until the chlorhexidinearticle is applied to a skin or a mucous membrane of a patient todisinfect the skin or the mucous membrane.
 12. The sterilizedchlorhexidine product of claim 10, wherein the antiseptic compositioncomprises between 2.0% and 10% of chlorhexidine gluconate based on atotal weight of the antiseptic composition.
 13. The sterilizedchlorhexidine product of claim 10, wherein the antiseptic compositionfurther comprises one or more of purified water, isopropyl alcohol,glycerol, and propylene glycol.
 14. The sterilized chlorhexidine productof claim 10, wherein the antiseptic composition further comprises anemollient comprising one or more of dimethicone, alkyl methicones, alkyldimethicones, phenyl silicones, and alkyl trimethylsilanes.
 15. Thesterilized chlorhexidine product of claim 10, wherein the chlorhexidinearticle comprises the antiseptic composition in an amount between 0.1and 2.5 grams.
 16. A method of using a sterilized chlorhexidine articlefor topical disinfection, the method comprising: providing a sterilizedchlorhexidine product for topical disinfection, comprising: a package;and at least one sterilized chlorhexidine article comprising a cloth;wherein the package comprises: a film defining an interior volume, thesterilized chlorhexidine article disposed within the interior volume; afirst sealed end portion positioned at a first end of the film; and asecond sealed end portion positioned at a second end of the film;wherein the first sealed end portion and the second sealed end portiondefine a hermetically sealed portion about the interior volume; openingthe package to access the at least one sterilized chlorhexidine article;applying the sterilized chlorhexidine article to a patient's skin fordisinfecting skin or mucous membranes of the patient.
 17. The method ofclaim 16, wherein opening the package comprises breaking a tear portionon the first end portion or the second end portion, wherein the tearportion is configured to maintain the hermetically sealed portion untilthe tear portion is broken.
 18. The method of claim 16, whereinproviding the sterilized chlorhexidine product comprises providing twochlorhexidine articles.
 19. The method of claim 16, wherein thesterilized chlorhexidine article comprises an antiseptic composition andwherein the antiseptic composition comprises between 2.0% and 10% ofchlorhexidine gluconate based on a total weight of the antisepticcomposition.
 20. The method of claim 16, wherein the sterilizedchlorhexidine article comprises an antiseptic composition in an amountbetween 0.1 and 2.5 grams.